Social determinants of fatty liver disease and its racial/ethnic disparities: The Multi-Ethnic Study of Atherosclerosis

项目摘要 肝病死亡率是最近美国预期寿命下降的关键因素。几十年的 研究表明，少数种族/民族的肝病负担不成比例， 社会经济地位低的人。随着肥胖症的流行和酒精的增加 脂肪性肝病（FLD），包括非酒精性脂肪性肝病（NAFLD）和酒精相关性肝病。 肝病（ALD）已成为影响数百万人的最普遍的慢性肝病 这在世界范围内构成了一个重大且日益严重的公共卫生问题。FLD流行病学主要集中在 个体水平的行为因素，如肥胖和饮酒，在FLD发展中的作用。 然而，以个人为重点的治疗和预防努力取得的成功有限。对于许多慢性 除了疾病之外，大量文献记载了社会和物理环境如何影响人口健康。 相反，社会决定因素在FLD及其差异中的作用的经验证据是 极其有限。此外，目前解释FLD差异的范式主要集中在遗传上， 易感性（例如PNPLA 3基因变体）。 为了填补这些研究空白，该项目将测试新的假设，即个人和社区- 水平的社会决定因素影响FLD风险及其社会和种族/民族差异。为了验证这个假设， 我们建议获得并分析参与者肝脏脂肪和炎症的纵向测量结果， 多种族动脉粥样硬化研究（梅萨），正在进行的最大的多种族人群队列研究 涉及来自6个地理区域的6，814名男性和女性（22%西班牙裔，38%白人，28%黑人，12%中国人） 美国的不同地区。梅萨拥有最全面的社会经济纵向数据（包括个人数据）。 和社区水平），心理社会，邻里物理和社会环境，环境，行为， 生物医学（包括遗传学）因素和健康结果，随访时间长达21年。我们的具体 目的是：1）描述FLD发病率的种族/民族差异，通过CT的10年变化来衡量， 测量肝脂肪和肝酶，同时考虑遗传变异。2)检查预期 个人社会经济地位（SEP）和心理社会压力与FLD发病率的关系， SEP和心理社会因素对FLD发病率的社会经济和种族/民族差异的贡献。 3)检查社区水平的社会和身体特征与FLD发病率的前瞻性关联， FLD发病率的种族/民族差异。4)审查社区一级社会和自然特征的作用 在放大个人层面的遗传脆弱性，通过测试基因与环境的相互作用， 遗传变异和环境因素之间的FLD。这个项目将构成美国历史上规模最大， 全面调查健康的社会决定因素在发展和进步中的作用， 的差距和差距。

PROJECT SUMMARY Liver disease mortality is a key contributor to recent declines in life expectancy in the US. Decades of research have demonstrated the disproportionate burden of liver disease among racial/ethnic minorities and those with low-socioeconomic position. With the ongoing epidemic of obesity, and the increase in alcohol consumption, fatty liver diseases (FLD), including non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), have become the most prevalent chronic liver conditions affecting millions of people worldwide, constituting a major and growing public health problem. FLD epidemiology has largely focused on the role of individual-level behavioral factors, such as obesity and alcohol consumption, in FLD development. However, individual-focused therapeutic and preventive efforts have had limited success. For many chronic diseases, abundant literature has documented how social and physical environments pattern population health. In contrast, the empirical evidence of the role of social determinants of health with FLD and its disparities is extremely limited. Furthermore, the current paradigm to explain FLD disparities is heavily focused on genetic susceptibility (e.g. PNPLA3 gene variants). To address these research gaps, this project will test the novel hypothesis that individual and community- level social determinants influence FLD risk and their social and racial/ethnic disparities. To test this hypothesis, we propose to obtain and analyze longitudinal measures of liver fat and inflammation among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), the largest ongoing multi-racial population-based cohort study involving 6,814 men and women (22% Hispanic, 38% whites, 28% Blacks, 12% Chinese) from 6 geographically distinct areas of the US. MESA has the most comprehensive longitudinal data on socioeconomic (both individual and community level), psychosocial, neighborhood physical and social environment, environmental, behavioral, and biomedical (including genetics) factors and health outcomes with up to 21 years of follow up. Our specific aims are: 1) Characterize racial/ethnic disparities in FLD incidence, as measured by 10-year changes in CT- measured liver fat and liver enzymes, while accounting for genetic variants. 2) Examine the prospective association of individual-level socioeconomic position (SEP) and psychosocial stressors with FLD incidence and the contribution of SEP and psychosocial factors to socioeconomic and racial/ethnic disparities in FLD incidence. 3) Examine the prospective association of community-level social and physical features with FLD incidence and its racial/ethnic disparities in FLD incidence. 4) Examine the role of community-level social and physical features in magnifying individual-level genetic vulnerability by testing gene-by-environment interactions in the incidence of FLD between genetic variants and contextual factors. This project will constitute the largest, most rigorous and comprehensive investigation of the role of social determinants of health in the development and progression of FLD and its disparities.